{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:13:38Z","timestamp":1790802818514,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T00:00:00Z","timestamp":1764028800000},"content-version":"vor","delay-in-days":24,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Rheum Dis"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n \n Rheumatoid arthritis (\n RA<\/jats:styled-content>\n ) is a complex autoimmune disease influenced by genetic and immune dysregulation. The causal roles of specific immune\u2010related genes in\n RA<\/jats:styled-content>\n pathogenesis remain incompletely understood.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n We conducted a large\u2010scale genome\u2010wide association study (\n GWAS<\/jats:styled-content>\n ) meta\u2010analysis across three\n RA<\/jats:styled-content>\n cohorts to identify genome\u2010wide significant risk loci. Causal genes and proteins were prioritized by integrating these results with cis\u2010\n eQTL<\/jats:styled-content>\n and\n pQTL<\/jats:styled-content>\n datasets using two\u2010sample Mendelian randomization (\n MR<\/jats:styled-content>\n ) and summary\u2010data\u2010based\n MR<\/jats:styled-content>\n (\n SMR<\/jats:styled-content>\n ). Cell\u2010type\u2010specific expression was assessed using single\u2010cell\n RNA<\/jats:styled-content>\n sequencing (\n scRNA<\/jats:styled-content>\n \u2010seq), and gene expression in\n RA<\/jats:styled-content>\n synovial tissue was validated via bulk\n RNA<\/jats:styled-content>\n \u2010seq.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n We identified 29 independent\n RA<\/jats:styled-content>\n \u2010associated loci, including 7 novel associations. Integrated\n MR<\/jats:styled-content>\n and\n SMR<\/jats:styled-content>\n analyses classified\n ERAP2<\/jats:styled-content>\n as a high\u2010confidence causal gene, while\n SWAP70<\/jats:styled-content>\n and\n LTBR<\/jats:styled-content>\n were deemed moderate\u2010confidence causal genes.\n SWAP70<\/jats:styled-content>\n showed a protective association, whereas\n ERAP2<\/jats:styled-content>\n and\n LTBR<\/jats:styled-content>\n were positively associated with\n RA<\/jats:styled-content>\n risk. Single\u2010cell transcriptomic analysis revealed cell\u2010type\u2010specific enrichment, with\n SWAP70<\/jats:styled-content>\n prevalent in B cells and\n LTBR<\/jats:styled-content>\n in dendritic cells. Bulk\n RNA<\/jats:styled-content>\n \u2010seq confirmed the upregulation of\n SWAP70<\/jats:styled-content>\n ,\n RASGRP1<\/jats:styled-content>\n , and\n RHOH<\/jats:styled-content>\n in\n RA<\/jats:styled-content>\n patients.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our integrative multi\u2010omics framework reveals immune regulatory genes with potential causal roles in\n RA<\/jats:styled-content>\n pathogenesis, highlighting\n ERAP2<\/jats:styled-content>\n ,\n SWAP70<\/jats:styled-content>\n ,\n LTBR<\/jats:styled-content>\n , and other candidates as promising therapeutic targets.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/1756-185x.70479","type":"journal-article","created":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T08:41:33Z","timestamp":1764060093000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genome\u2010Wide Association Analysis and Multi\u2010Omic Mendelian Randomization Insight Into the Molecular Network of Immune\u2010Related Dysfunction in the Pathogenesis of Rheumatoid Arthritis"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0642-7170","authenticated-orcid":false,"given":"Xiaohong","family":"Song","sequence":"first","affiliation":[{"name":"Department of Blood Transfusion The Third Xiangya Hospital, Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion The Third Xiangya Hospital, Central South University Changsha Hunan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Blood Transfusion The Third Xiangya Hospital, Central South University Changsha Hunan 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